The biochemistry and ultrastructure of the title subject is reviewed with concentration on the periplasmic space - the region between the protoplasmic membrane and the cell wall. Recent papers by the principal investigators describe periplasmic bodies (P.B.) in young cells of S.rouxii. The presence of these membrane-circumscribed, electron-dense organelles is associated with crypticity of beta-fructofuranosidase, a normal periplasmic enyzme which is, however, fully expressed in most other yeasts. Unpublished evidence is presented to show that P.B. originate from the transport stage. Lysis of periplasmic bodies (aging) gives final deposition in the periplasmic space and, simultaneously, expression. S. rouxii seems unique in the longevity of its P.B. P.B.-like Vesicles are seen in a variety of pathogenic and non-pathogenic yeasts under aberrant growth conditions. A challenge with fungistatic concentrations of polyenes leads to formation of P.B. Our hypothesis is that a second function of P.B. is to sequester segments of denatured membrane (e.g. sterols complexed with polyenes). This program will develop the methodology for the release and purification of P.B. from S. rouxii by cell wall digestion, followed by density gradient centrifugations. The physical, chemical, and enzymic properties of P.B. will be compared with naked protoplasts. We will optimize conditions for P.B. formation in Candida albicans and Histoplasma capsulatum under Amphotericin B, Nystatin, and Filipin treatments. We will isolate P.B. from these treated cells, and membrane fractions prepared by lysis will be analyzed for all classes of lipids and for polyenes. Our hypothesis suggests an enrichment in polyenes and a higher sterol: phospholipid ratio in P.B. membranes. Compounds which interfere with P.B. formation will be tested for enhancing the lethality of polyenes which are nephrotoxic in high concentrations.